Single channels activated by high concentrations of GABA in superior cervical ganglion neurones of the rat. 1991

C F Newland, and D Colquhoun, and S G Cull-Candy
Department of Pharmacology, University College London.

1. Single-channel currents evoked by high concentrations of GABA (10-2000 microM) have been analysed to investigate the characteristics of GABAA receptor channels in outside-out patches from rat sympathetic neurones. When high concentrations of GABA were applied to a patch, channel openings occurred in prolonged clusters (3.8 +/- 3.7 s (mean +/- S.D.) at 50 microM-GABA) consisting, on average, of 350 apparent openings per cluster. Individual clusters were separated by long silent intervals. 2. Channel openings were to many (often ill-defined) conductance states (range 7-36 pS), but the most frequently observed conductance level was approximately 30 pS, (29.6 +/- 0.34 pS). Only these clusters during which the channel was open to this main state conductance for at least 95% of the cluster open time were used in the analysis of probability of being open. Other less frequently observed conductance levels were 15-18 and 22-23 pS, while levels of 33-36 and 7-9 pS were occasionally, but reliably, observed. 3. Bursts within clusters were defined as a series of openings separated by closed intervals shorter than some critical value, tc. At 50 microM-GABA the mean burst length was 439 +/- 434 ms (+/- S.D., tc = 50 ms). 4. The probability of being open, po, during bursts within clusters has been analysed as a function of GABA concentration. As expected, increasing the concentration of GABA resulted in an overall increase in po. However, for a given agonist concentration there was a wide spread in po, far greater than that predicted for a population of identical and independent receptor channels (demonstrated by comparison with stimulated channel activity). 5. The wide range of po values at a particular concentration of GABA was not due to inappropriate selection of tc. At 50 microM-GABA the range of po values was similar for tc of 20-1000 ms, although the overall mean po became lower (0.64 rather than 0.81). 6. On the basis of simulated channel activity, it appears that most clusters which do not contain multiple openings, arise from the activity of one individual channel. Furthermore, there was no detectable tendency for gaps between bursts to be shorter in the middle of a cluster than at its ends. Therefore it is unlikely that variability in po arose from overlapping activity of two or more channels. 7. The values for po, mean open time, and mean shut time for bursts within the same cluster, and between different clusters, were compared by a randomization test.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D011336 Probability The study of chance processes or the relative frequency characterizing a chance process. Probabilities
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260 Female Females
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D005728 Ganglia, Sympathetic Ganglia of the sympathetic nervous system including the paravertebral and the prevertebral ganglia. Among these are the sympathetic chain ganglia, the superior, middle, and inferior cervical ganglia, and the aorticorenal, celiac, and stellate ganglia. Celiac Ganglia,Sympathetic Ganglia,Celiac Ganglion,Ganglion, Sympathetic,Ganglia, Celiac,Ganglion, Celiac,Sympathetic Ganglion
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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